Colon cancer, which affects men and women equally, is the second most common cause of cancer death in the U.S. The overall goal of the colon cancer program is the prevention of this malignancy through understanding its biology and pathogenesis. The adenomatous polyp, the precursor of colon cancer, is a central theme of our investigations both as a clinical and biologic marker of colon cancer risk and development. The program includes a broad spectrum of integrated projects ranging from the most basic genetic and biologic studies to clinical screening and prevention investigations. Under a translational structure, investigators will: clinically and genetically define familial risk of colon cancer, determine the cellular mechanisms of APC protein function; determine the cellular consequences and mechanisms and effects of cyclo- oxygenase over-expression in normal colonic and neoplastic tissues; examine genetic-environmental interactions in the pathogenesis of colon cancer; and test chemoprevention agents against GI neoplasms. A supporting infrastructure has been developed to accomplish this work which includes: a familial colon cancer clinical and registry, a genetic counseling service, a general CRC with endoscopic capabilities, a population data base for access of familial cases, and a regional gastroenterology network for access and care of patients.